Abstract

The prevalence of obesity has nearly doubled worldwide over the past three decades,
but substantial differences exist between nations. Although these differences are
partly due to the degree of westernization, genetic factors also contribute. To date,
little is known about whether the same genes contribute to obesity-susceptibility
in populations of different ancestry. We review the transferability of obesity-susceptibility
loci (identified by genome-wide association studies) using both single nucleotide
polymorphism (SNP) and locus-wide comparisons. SNPs in FTO and near MC4R, obesity-susceptibility loci first identified in Europeans, replicate widely across
other ancestries. SNP-to-SNP comparisons suggest that more than half of the 36 body
mass index-associated loci are shared across European and East Asian ancestry populations,
whereas locus-wide analyses suggest that the transferability might be even more extensive.
Furthermore, by taking advantage of differences in haplotype structure, populations
of different ancestries can help to narrow down loci, thereby pinpointing causal genes
for functional follow-up. Larger-scale genetic association studies in ancestrally
diverse populations will be needed for in-depth and locus-wide analyses aimed at determining,
with greater confidence, the transferability of loci and allowing fine-mapping. Understanding
similarities and differences in genetic susceptibility across populations of diverse
ancestries might eventually contribute to a more targeted prevention and customized
treatment of obesity.